Angiogenic potential in the aging heart is depressed. Preliminary studies have revealed that alterations in endothelial cells contribute to this decline in senescent cardiac angiogenic activity. Recent studies have also demonstrated that the bone marrow is a source of endothelial precursor cells as well as other vascular cell types that may contribute to the regulation of angiogenic activity. Therefore as one approach to study the depression in senescent cardiac angiogenic potential, we have employed bone marrow transplantation as a means of restoring cell populations that are critical in the regulation of cardiac angiogenesis in the aging host. Specifically, it was shown that when transplanted with the bone marrow of young mice (3 months old), the senescent mice (18 months old) had a marked improvement in their cardiac angiogenic potential. These preliminary data strongly support the hypothesis that a specific subpopulation(s) of bone marrow derived cells can restore senescent cardiac angiogenic potential. The long-range goals of this project are to enhance to angiogenic activity in the aging heart employing molecular and/or cellular approaches specifically directed at the distinct subpopulation(s) of bone marrow- derived cells that are critical in the restoration of senescent cardiac angiogenic activity. Using a combination of histological and proteomic approaches in conjunction with bone marrow transplantation into senescent marine hosts we will identify the cell types and characterize the surface epitopes of the bone marrow derived cells that are recruited to cardiac angiogenic foci in the aging host. The results of these studies will then be incorporated into future studies designed to identify the molecular and cellular actions mediating the restoration of senescent cardiac angiogenic potential. Moreover, these studies will establish a basis for the development of novel approaches directed at improving vascular function in the aging heart.